Highly Diastereo‐ and Enantioselective Direct Aldol Reactions in Water

Abstract

Grüne Chemie: Aldolreaktionen, die in vielen Synthesen eine wichtige Rolle spielen, verlaufen auch in Wasser und ohne Metallkatalysator mit ausgezeichneten Enantioselektivitäten. Entscheidend für diese umweltverträgliche Synthese chiraler Verbindungen ist ein synthetischer Organokatalysator mit trans‐Hydroxyprolin‐Gerüst und einer Siloxygruppe (siehe Bild; TBDPS=tert‐Butyldiphenylsilyl).

Novel Prolinamide‐Supported Polystyrene as Highly Stereoselective and Recyclable Organocatalyst for the Aldol Reaction

“…Substituted prolinamides have been recently found to be active and highly stereoselective catalysts for direct aldol reaction in aqueous medium. [9] Indeed, since 2006, when Barbas [10] and Hayashi [11] independently reported the highly stereoselective aldol reactions using proline derivatives as organocatalysts in the presence of water, [12] this point has received attention. [13] Particularly, compound 1 (Figure 1) gave excellent results in the direct aldol reaction.…”

Enantioselective Michael Addition of Dicyanoolefins to α,β‐Unsaturated Aldehydes in Aqueous Medium

“…Just recently, breakthrough contributions were made by the groups of Barbas, [4] Takabe, [4] and Hayashi. [5] They used proline-derived catalysts in the presence of water to demonstrate the direct asymmetric aldol reaction and the Michael reaction with high yields and with excellent diastereoselectivities and enantioselectivities. Thereafter, many organocatalysts have been designed for different enantioselective reactions under aqueous conditions, for example, chiral dialkylprolinol derivatives have been applied in asymmetric conjugate additions to provide high enantioselectivities using water as the only solvent.…”

The Ion Tag Strategy as a Route to Highly Efficient Organocatalysts for the Direct Asymmetric Aldol Reaction

“…[7] In 2006 the field of enantioselective organocatalytic aldol and related reactions in water recorded an exceptional breakthrough, with the contributions reported by Barbas and co-workers, [7,8] Hayashi and coworkers, [9] and other groups. [10] The key to success was to develop heterogeneous aqueous biphasic conditions which simulated the hydrophobic pocket where class I aldolases are supposed to promote their aldol reactions through the so called "asymmetric aminocatalysis".…”

“…[9] A slightly different approach combined partially water-soluble catalysts with salts that facilitate hydrophobic aggregation by "salting out". [12] The result was on outstanding increase of the reaction efficiency ex-pressed as TONs.…”